Photosensitization can result when light interacts with endogenous or exogenous chemical agents in the skin and other tissues. This process can produce undesirable clinical consequences, as in phototoxicity and photoallergy; or it can have beneficial effects, as in tumor photodynamic therapy (PDT) and coal-tar or psoralen (PUVA) therapy against psoriasis. Photosensitization results from the light-induced production of free radicals and/or singlet oxygen (102), the lowest electronic excited state of molecular oxygen. Because the latter species may be important in both phototoxic reactions and PDT, we have developed state-of-the-art instrumentation capable of detecting the characteristic phosphorescence of 102 at 1268 nm. We are also establishing a flash photolysis facility which permits us to monitor triplet- excited state activity of potential photosensitizers. This has permitted us to delineate the photophysics of 102 production in solution by a number of chemicals with photosensitizing activities in vivo, including phenothiazine derivatives (e.g., promazine (PZ) and chlorpromazine (CPZ)), benzoxazole analogs (e.g., benoxaprofen (BP)), tetracyclines, anthrapyrazoles, anthracene, anthralin, anthraquinones, and hematoporphyrin derivative. We have shown, for example, that, when they are excited with light, PZ and CPZ sensitize significant 102 production in organic solvents (the quantum yield, phi varies between 0.1 and 0.4 depending on the solvent) but they do not sensitize detectable amounts of 102 in water (phi less than 0.01). Another drug, BP, also sensitizes very little 102 production in water (phi less than 0.01); however, its decarboxylated photoproduct is lipid soluble and efficiently produces 102 in organic solvents. We have also demonstrated that upon irradiation Merocyanine 540, currently used to destroy tumor cells in bone marrow explants, produces 102 in liposomes and that anthracene, eosin gamma and hematoporphyrin derivative produce 102 in erythrocyte ghosts.